Abstract
Preterm birth (PTB; birth before 37 completed weeks of gestation) remains the major cause of neonatal morbidity and mortality. The current generation of biomarkers predictive of PTB have limited utility. In pregnancy, the human cervicovaginal fluid (CVF) proteome is a reflection of the local biochemical milieu and is influenced by the physical changes occurring in the vagina, cervix and adjacent overlying fetal membranes. Term and preterm labor (PTL) share common pathways of cervical ripening, myometrial activation and fetal membranes rupture leading to birth. We therefore hypothesize that CVF biomarkers predictive of labor may be similar in both the term and preterm labor setting. In this review, we summarize some of the existing published literature as well as our team's breadth of work utilizing the CVF for the discovery and validation of putative CVF biomarkers predictive of human labor. Our team established an efficient method for collecting serial CVF samples for optimal 2-dimensional gel electrophoresis resolution and analysis. We first embarked on CVF biomarker discovery for the prediction of spontaneous onset of term labor using 2D-electrophoresis and solution array multiple analyte profiling. 2D-electrophoretic analyses were subsequently performed on CVF samples associated with PTB. Several proteins have been successfully validated and demonstrate that these biomarkers are associated with term and PTL and may be predictive of both term and PTL. In addition, the measurement of these putative biomarkers was found to be robust to the influences of vaginal microflora and/or semen. The future development of a multiple biomarker bed-side test would help improve the prediction of PTB and the clinical management of patients.
Highlights
A human pregnancy has a gestational period between 37 and 42 weeks
Pereira et al (2007) compared the cervicovaginal fluid (CVF) proteome between three groups of women: symptomatic women admitted with threatened Preterm Labor (PTL) who delivered preterm, symptomatic women in “false” labor who delivered at term and asymptomatic gestationmatched controls
Nine proteins (ANXA3, cystatin A (CSTA), FABP5, GC, GGCT, interleukin-1 receptor antagonist (IL1RN), SERPINB1, SERPINB3, and TXN) were differentially expressed in asymptomatic women (n = 5) 6– 23 days before preterm Pre-labor Rupture of Membranes (PROM) and delivered preterm compared to gestation-matched controls who delivered at term (n = 10) (Liong et al, 2013b)
Summary
A human pregnancy has a gestational period between 37 and 42 weeks. Births before 37 completed weeks of gestation are classified as preterm. Given the challenges of preventing PTB, the ability to reliably predict who will deliver preterm may aid in the clinical management of asymptomatic or symptomatic women (i.e., in threatened PTL with uterine contractions without cervical dilatation). Other Biochemical Markers Given the poor sensitivity of the fFN and phIGFBP1 tests to predict spontaneous PTB in the asymptomatic pregnant population, researchers have investigated alternative biomarkers associated with PTL and assessed their predictive utility. The evaluation of these putative biomarkers indicates that no single biomarker is superior in predicting spontaneous PTB (Wei et al, 2010; Conde-Agudelo et al, 2011; Menon et al, 2011; Bhat et al, 2013), perhaps reflecting the different aetiologies associated PTL. The biochemical tests continue to be unreasonably expensive but can provide valuable reassurance (negative likelihood) for the symptomatic woman from a remote community where neonatal intensive care facilities are not available
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